Hepatitis B virus, a small DNA virus, is the prototype of the Hepadnaviridae family. Chronic infection with HBV (CHB) remains a significant public health problem in worldwide, which is a major factor resulting in fibrosis, cirrhosis, and hepatocellular. Previous HBV treatment devote to interfere the HBV genome, including nucleotide analogues (NAs) and type Ⅰ interferon (IFN). However, virus mutation and drug resistance occur during these treatments. And current therapeutic strategy tend to intervene the host factors, involvement in the entry, replication and assemble of HBV, bringing us a new venue against HBV. Thus, numerous studies spent large amount efforts to explore RNA interference (RNAi) host gene silencers, which potentially could be a novel anti-HBV therapeutics. Here, we summarized the current progression targeting the host genes for curing chronic HBV infection.